Grant Abstract

Abstract: This career development application proposes an integrated research and training plan to develop expertise in assessing mild cognitive impairment and measuring brain structures, particularly the hippocampus, in older adults. The specific aims of the application are to determine whether vitamin D deficiency is related to worse cognitive performance, depressive symptoms and/or decreased hippocampal volumes. The long-term objectives are to provide training and education to facilitate the applicant's transition to an independent patient-oriented investigator. The proposed research and training will provide the applicant with skills in designing and implementing longitudinal studies and with valuable techniques in stereological estimation methods to measure brain volumes. Upon completion of the award, the applicant will have the necessary skills to design, obtain funding, and implement original research studies to understand biologic mechanisms important in cognitive function in older adults. As Alzheimer's disease continues to be a major medical and social challenge, research in this field increasingly focuses on detecting the very earliest signs of cognitive impairment. As many investigate approaches to diagnose and prevent mild cognitive impairment in older adults, the relationship between depressive symptoms and mild cognitive impairment has been less studied. Recent data find an association between depression and very mild cognitive impairment. The combination of cognitive and depression increases the likelihood of institutionalization, increases caregiver burden and decreases survival. It is therefore important to identify risk factors that may affect both cognition and mood. One potential risk factor is vitamin D deficiency, which is associated with falls and fractures, affective disorders, and also has roles in neuroprotection and brain development. Vitamin D is a potent inducer of nerve growth factor and in animal studies has reversed brain injury due to various insults. Although more than half of older adults have vitamin D deficiency, few are treated. This is partly due to the lack of data supporting a role for vitamin D in nonbone related disorders. This application will investigate important relationships between vitamin D deficiency, cognitive function and mood all of which result in excess disability in the elderly.